E.coli has been turned into a biological hard drive

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If you want to get reductionist about it, a cell is just a really complex, squishy, water-logged robot. That’s the basic idea behind synthetic biology, that by understanding the parts and manufacturing of a biological organism we can use it as a tool for our own selfish purposes. Of course, the first stabs at actually applying this idea were purely practical: put biological workers in a car’s gas tank to make ethanol, or in a landfill to eat harmful garbage, or in the ocean to combat acidification. However, a huge proportion of modern robots are probes or observers that collect information and report it back to us, and that’s one area in which biology has always lagged behind — but that might be about to change.

A team from MIT has published a remarkable study in which they give their e.coli bacteria memory, a hard drive of sorts for a biological machine. Since single celled organisms can’t remember and repeat information, though, that memory comes in the form of DNA, as the cells physically restructure their own genomes to record outside events. This occurs thanks to their core innovative technique called SCRIBE, or Synthetic Cellular Recorders Integrating Biological Events, which inserts a genetic marker into the cell’s genome whenever a prescribed signal is received — and that signal can be almost anything. The team says they haven’t just invented a binary, yes-no bacterial switch, but a modular recorder that can show the strength and distribution of a signal as well.

It all works thanks to poorly understood genetic structures called retrons. Retrons are free-floating genetic factories (that is, not bound to the chromosomes that contain the vast majority of genetic information) that make RNA molecules along with the enzyme which turns them into DNA. Just why returns do this in normal cells is an open question, but we don’t need to answer it to see the utility they could offer in engineered ones; by programming retrons to create a specified stretch of DNA in response to a chemical signal (say, a particular contaminant in the water around the cell), the team had their response mechanism — but still no memory.

An enzyme called recombinase fixes this problem by inserting the new retron DNA strands into the bacteria’s genome at a specific site, chosen by the experimenters. So, the signal stimulates creation of the marker DNA sequence, which is then inserted into the genome at a marker location. This is now a complete binary switch present in each individual cell, and sequencing a colony’s DNA will show the researchers whether that particular cell was exposed to the signal or not. The analog aspect comes thanks to the incredible numbers of bacteria in a culture; any one cell by itself can offer only a yes-no answer to a scientist’s chemical question, but the proportion and distribution of those positive and negatives answers among a billions-strong bacterial population can reveal a lot more. Finding any yes responses at all reveals the presence of your contaminant, while the number of them reveals its rough concentration.

By inserting their marker sequence into the genome of the cell, they ensure that the sequence will be preserved, even across multiple generations. This means you could “infect” a water tower with a benign e.coli robo-species and allow it to sustain itself as a long-term early warning mechanism. Life can be far more resilient and long-lasting than computerized probes, especially in certain environments; even if we have literal robots that could enter our bloodstream and search out medical info, many bacterial species have evolved specifically to thrive there. Bacterial robots could end up bypassing a lot of potential problems by leveraging the fixes evolution has provided for us.

What’s most interesting is that the team can insert their marker DNA into the genome so as to make sequencing unnecessary for many simple tests; engineer your cells so a particular antibiotic resistance gene is only turned on if the signal DNA is inserted into its genome, then treat this population with the antibiotic in question. Those colonies that survive are the ones with their resistance switched on, and thus arise from cells that received the signal we’re looking for. They could even have build-up mechanisms to show how long a signal lasted, for instance with an inserted marker sequence then activating a second retron that could be activated to insert a second marker, which in turn activates a third retron, and so on.

Fluorescent genes can be very noticeable, even to the naked eye.

And what sorts of signals might we look for with these bacterial information gatherers? The team can imagine everything from water purity guardians responding to signals from other, harmful bacteria to light-sensitive bacteria that take a marker sequence every time they’re exposed to UV radiation. The possibilities are almost endless, as all the team needs to put SCRIBE to work is some unambiguous input to flip their switch. Bacterial reporters could enter your bloodstream for a day or so, then get sequenced when your doctor takes a blood sample. They could be put into a sample of fertilizer and coded to fluoresce at night so farmers can immediately notice the arrival of some new pest species.

More to the point, we could use the SCRIBE technique — permanent genome editing via retrons — far more widely than just programming genetic storage. It’s a powerful tool in scientists’ toolbox, the sort of breakthrough that is finally allowing genetic engineering to deliver on some of the headlines of old. Detailed genetic manipulation of this sort will allow an increasingly wide array of functions from biological creatures, and further blur the line between robots made of metal and ones made of meat.